Brentuximab Vedotin, Plus Nivolumab, Doxorubicin, Dacarbazine Investigated for Classical Hodgkin Lymphoma

A phase 2 study in advanced classical Hodgkin lymphoma (cHL) treatment found encouraging response, survival, and safety results with brentuximab vedotin plus nivolumab, doxorubicin, and dacarbazine. The findings were published in Blood.

The study’s first author, Hun Ju Lee, MD, from MD Anderson Cancer Center, Houston, Texas, wrote with colleagues that the tested combination “continues to show a tolerable safety profile, with no new safety signals, along with a high CR [complete response] rate, ORR [objective response rate], and encouraging DOR [duration of response] that will continue to evolve with long-term follow-up.”

Explaining the impetus for the study, the authors wrote that recent trials which have compared the standard of care polytherapy for advanced cHL, doxorubicin hydrochloride plus bleomycin sulfate, vinblastine sulfate, and dacarbazine, with the test combination brentuximab vedotin plus vinblastine, doxorubicin, and dacarbazine, have found the latter produces better overall survival but worse adverse events (AE). Therefore, the authors sought to determine if replacing vinblastine in the test combination with nivolumab would remedy safety, as well as further improve efficacy.

Lee and colleagues elaborated that “combining IO [immune-oncology] agents, such as antibody-drug conjugates and PD-1 inhibitors, with chemotherapy may eliminate the need for vinblastine and bleomycin in treating cHL.”

The open-label multicenter study involved a cohort of 57 patients with untreated stage 2 bulky or 3/4 cHL. They received up to a maximum of six cycles of the test combination, with optional use of granulocyte-colony stimulating factor (G-CSF). The cohort had a median follow-up of 24.2 months.

With the test combination, the researchers calculated the patients had an ORR of 93% and a CR rate of 88%. Their 2-year progression-free survival rate was 88% and had a response that lasted for longer than 2 years.

Regarding safety and tolerability findings, there were no instances of febrile neutropenia in the study cohort. G-CSF prophylaxis was administered to 49% of patients. Treatment-related peripheral sensory neuropathy affected 44% of the total cohort; 40% had grade 1 or 2 and 4% had grade 3 severity neuropathy. The most common grade 3 or worse severity treatment-related AEs were alanine aminotransferase elevation and neutropenia, which affected 11% and 9% of the patients, respectively.

“These results warrant further investigation of PD-1 inhibitor and CD30 antibody-drug conjugate combination regimens in a larger study in advanced cHL,” Lee and colleagues concluded.

Reference

Lee HJ, Ramchandren R, Friedman J, et al. Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine for advanced-stage classical Hodgkin lymphoma. Blood. 2025;145(3):290-299. doi:10.1182/blood.2024024681